The microbiome in patients with atopic dermatitis.

As an interface with the environment, the skin is a complex ecosystem colonized by many microorganisms that coexist in an established balance. The cutaneous microbiome inhibits colonization with pathogens, such as Staphylococcus aureus, and is a crucial component for function of the epidermal barrier. Moreover, crosstalk between commensals and the immune system is now recognized because microorganisms can modulate both innate and adaptive immune responses. Host-commensal interactions also have an effect on the developing immune system in infants and, subsequently, the occurrence of diseases, such as asthma and atopic dermatitis (AD). Later in life, the cutaneous microbiome contributes to the development and course of skin disease. Accordingly, in patients with AD, a decrease in microbiome diversity correlates with disease severity and increased colonization with pathogenic bacteria, such as S aureus. Early clinical studies suggest that topical application of commensal organisms (eg, Staphylococcus hominis or Roseomonas mucosa) reduces AD severity, which supports an important role for commensals in decreasing S aureus colonization in patients with AD. Advancing knowledge of the cutaneous microbiome and its function in modulating the course of skin disorders, such as AD, might result in novel therapeutic strategies

Commensal Microbes and Hair Follicle Morphogenesis Coordinately Drive Treg Migration into Neonatal Skin

Regulatory T cells (Tregs) are required to establish immune tolerance to commensal microbes. Tregs accumulate abruptly in the skin during a defined window of postnatal tissue development. However, the mechanisms mediating Treg migration to neonatal skin are unknown. Here we show that hair follicle (HF) development facilitates the accumulation of Tregs in neonatal skin and that upon skin entry these cells localize to HFs, a primary reservoir for skin commensals. Further, germ-free neonates had reduced skin Tregs indicating that commensal microbes augment Treg accumulation. We identified Ccl20 as a HF-derived, microbiota-dependent chemokine and found its receptor, Ccr6, to be preferentially expressed by Tregs in neonatal skin. The Ccl20-Ccr6 pathway mediated Treg migration in vitro and in vivo. Thus, HF morphogenesis, commensal microbe colonization, and local chemokine production work in concert to recruit Tregs into neonatal skin, thereby establishing this tissue Treg niche early in life

Establishing Tolerance to Commensal Skin Bacteria Timing Is Everything

Commensal bacteria live intimately and in constant dialogue with skin immune cells. Regulating our immune response to these bacteria is critical for skin homeostasis. Using a new murine model to track Staphylococcus epidermidis-specific T cells, we found that colonization during neonatal but not adult life led to S.epidermidis-specific immune tolerance. This tolerance protected against skin inflammation and was mediated by a wave of regulatory T cells entering neonatal skin. These findings provide new insight into how we establish a healthy symbiosis with commensal microbes and highlight avenues for future research to identify novel therapies for inflammatory skin disease

Early life host-microbe interactions in skin

Our skin is the interface through which we mediate lifelong interactions with our surrounding environment. Initial development of the skin's epidermis, adnexal structures, and barrier function is necessary for normal cutaneous microbial colonization, immune development, and prevention of disease. Early life microbial exposures can have unique and long-lasting impacts on skin health. The identity of neonatal skin microbes and the context in which they are first encountered, i.e., through a compromised skin barrier or in conjunction with cutaneous inflammation, can have additional short- and long-term health consequences. Here, we discuss key attributes of infant skin and endogenous and exogenous factors that shape its relationship to the early life cutaneous microbiome, with a focus on their clinical implications

Skin Commensal Antigens: Taking the Road Less Traveled

Although our knowledge of host-commensal interactions has increased exponentially, the mechanisms linking a specific commensal, its detection by the immune system, and its impact on tissue function are still often poorly understood. In a recent study in Cell, Linehan et al. dissect one of these interactions in the context of the skin, and demonstrate that Staphylococcus epidermidis antigens, presented through a non-classical pathway, drive the accumulation of CD8+ T cells that promote wound healing

What lives on our skin: ecology, genomics and therapeutic opportunities of the skin microbiome

Our skin is home to a rich community of microorganisms. Recent advances in sequencing technology have allowed more accurate enumeration of these human-associated microbiota and investigation of their genomic content. Staphylococcus, Corynebacterium and Propionibacterium represent the dominant bacterial genera on skin and illustrate how bacteria adapt to life in this harsh environment and also provide us with unique benefits. In healthy states, our skin peacefully co-exists with commensal bacteria while fending off potentially dangerous invaders. Disruption of this equilibrium, termed "dysbiosis", can result from changes in the composition of our skin bacteria, an altered immune response to them, or both and may be a driving factor in certain types of inflammatory skin disease. Engineering topical therapeutics to favourably influence the composition of our skin flora and optimize interactions with them represents a real therapeutic opportunity for the field of dermatology and warrants additional investigation into skin microbial ecology and disease mechanisms related to host-microbe dysbiosis